Antipsychotic agents are used not only for treating schizophrenia and problem behaviors associated with cerebrovascular diseases and senile dementia (e.g. aggressive behaviors, psychogenic excitement, ecdemomania or delirium). However, dopamine D.sub.2 receptor antagonists, prior art antipsychotic drugs, cause serious extrapyramidal diseases as side effects, which has been a serious problem.
On the other hand, recently found dopamine D.sub.4 receptors are similar to dopamine D.sub.2 receptors in structure and properties, but are utterly different from dopamine D.sub.2 receptors in intracerebral distributions. The intracerebral distribution of dopamine D.sub.4 receptors is such that they are present in a high concentrations in the corticocerebral frontal lobe concerned with the onset of schizophrenia and are present in a low concentration in the striatum concerned with the onset of extrapyramidal diseases. Accordingly, unlike dopamines D.sub.2 receptor antagonists, dopamine D.sub.4 receptor antagonists are very likely to become novel therapeutic agents of schizophrenia without extrapyramidal diseases as side effects (Nature, 350, 610-614 (1991); Nature, 358, 109 (1992); Nature, 365, 393 (1993); Nature, 365, 441-445 (1993)).
Among such compounds is included clozapine. It has been reported that the affinity of clozapine for dopamine D.sub.4 receptors is higher than that for dopamine D.sub.2 receptors (Nature, 350, 610-614 (1991)). It has also been reported that in a clinical investigation of clozapine, unlike dopamine D.sub.2 receptor, clozapine is effective on drug-resistant schizophrenia and negativism and hardly causes extrapyramidal diseases (Arch. Gen. Psych., 45, 789-796 (1988)). However, clozapine has a serious defect of causing blood disorder called agranulocytosis, and cases of death therefrom have been reported (Summary and Clinical Data, Sandoz, Canada Inc. (1990)).
Accordingly, dopamine D.sub.4 receptor antagonists without such side-effects are very useful as therapeutic agents of schizophrenia which are very unlikely to cause extrapyramidal diseases.
An object of the present invention is to provide dopamine D.sub.4 receptor antagonist compounds which have an antipsychotic action without causing extrapyramidal diseases.